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Psychiatry Research/Trial Protocols

Psychological treatments for mental health symptoms associated with COVID-19 infection: A scoping review
Sugita S, Hata K, Kodaiarasu K, Takamatsu N, Kimura K, Miller C, Gonzalez L, Umemoto I, Murayama K, Nakao T, Kito S, Ito M and Kuga H
The aim of this scoping review was to synthesize published studies and ongoing clinical trials of psychological interventions for mental health problems associated with COVID-19 infection. The study protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews. We conducted systematic searches for studies published or registered between January 2020 and October 2022 using eight scientific databases and clinical trial registries, which identified 40 complete published studies and 53 ongoing clinical trials. We found that most studies were randomized controlled trials (74%) while the remaining used study designs of lower methodological quality. Most studies investigated interventions for acute COVID-19 patients (74%) and others explored post-COVID conditions (PCC) or recovered patients. Cognitive and behavioral therapies were the main intervention approaches (31%), followed by multidisciplinary programs (21%) and mindfulness (17%). The most frequently evaluated outcomes were anxiety (33%), depression (26%), quality of life (13%), and insomnia (10%). No studies on youths, older people, or marginalized communities were found. These findings summarize the burgeoning research on a range of psychological interventions for individuals infected with COVID-19. However, the field is in its infancy and further research to develop an evidence base for targeted care is necessary. The gaps identified in the current study also highlight the need for more research on youths, older people, and members of marginalized communities, and PCC patients. It is important to ascertain interventions and delivery strategies that are not only effective and affordable but also allow high scalability and accessibility.
Efficient characterization of multiple binding sites of small molecule imaging ligands on amyloid-beta, tau and alpha-synuclein
Sobek J, Li J, Combes BF, Gerez JA, Henrich MT, Geibl FF, Nilsson PR, Shi K, Rominger A, Oertel WH, Nitsch RM, Nordberg A, Ågren H and Ni R
There is an unmet need for compounds to detect fibrillar forms of alpha-synuclein (αSyn) and 4-repeat tau, which are critical in many neurodegenerative diseases. Here, we aim to develop an efficient surface plasmon resonance (SPR)-based assay to facilitate the characterization of small molecules that can bind these fibrils.
Global prevalence of depression in chronic kidney disease: a systematic review and meta-analysis
Adejumo OA, Edeki IR, Sunday Oyedepo D, Falade J, Yisau OE, Ige OO, Adesida AO, Daniel Palencia H, Sabri Moussa A, Abdulmalik J, Noubiap JJ and Ekrikpo UE
Chronic kidney disease (CKD) is commonly associated with psychosocial problems, especially depression, contributing to poor overall outcomes. Depression has not been given adequate priority in the management of CKD patients despite its significant adverse impact on all major outcomes. This systematic review and meta-analysis determined the pooled prevalence of clinical depression in the global CKD population and sub-populations.
Walking the line between fidelity and flexibility: A conceptual review of personalized approaches to manualized treatments for posttraumatic stress disorder
Galovski TE, Nixon RDV and Kehle-Forbes S
The heterogeneity of the core symptoms of posttraumatic stress disorder (PTSD), high rates of comorbid mental and physical health conditions, and substantial impact of the disorder on functioning and well-being contribute to complex clinical presentations that can be challenging to treat. Despite these challenges, there are excellent manualized treatments for PTSD with significant empirical support. Although the success of frontline treatments for PTSD is evident, there remains room for improvement as indicated by suboptimal response and attrition rates. To address challenges to optimal therapy outcomes (COTOs), researchers have conducted numerous clinical trials designed to (a) enhance the core structure of treatment protocols to increase flexibility or (b) expand the protocols to address comorbid conditions that inhibit recovery. However, it is implausible to ever conduct the number of enhancement and expansion clinical trials necessary to test manual modifications for the universe of possible COTOs. This conceptual review describes the concept of a personalized model of therapy that leverages a case formulation approach to implementing an evidence-based treatment for PTSD. This personalized approach provides guidance for the clinician in assessing the patient's COTOs, monitoring them throughout treatment, and relying on the patient's idiosyncratic data to inform treatment decisions, including how and when to diverge from treatment when clinically indicated and ensuring a clear path to return to trauma-focused work when the COTO is stabilized. This personalized, case formulation approach to treating PTSD provides guidance for adopting a more flexible approach to treating clinically complex patients while ensuring fidelity to the protocol.
Just-in-time adaptive interventions for adolescent and young adult health and well-being: protocol for a systematic review
Guan KW, Adlung C, Keijsers L, Smit CR, Vreeker A, Thalassinou E, van Roekel E, de Reuver M, Figueroa CA and
Health behaviours such as exercise and diet strongly influence well-being and disease risk, providing the opportunity for interventions tailored to diverse individual contexts. Precise behaviour interventions are critical during adolescence and young adulthood (ages 10-25), a formative period shaping lifelong well-being. We will conduct a systematic review of just-in-time adaptive interventions (JITAIs) for health behaviour and well-being in adolescents and young adults (AYAs). A JITAI is an emerging digital health design that provides precise health support by monitoring and adjusting to individual, specific and evolving contexts in real time. Despite demonstrated potential, no published reviews have explored how JITAIs can dynamically adapt to intersectional health factors of diverse AYAs. We will identify the JITAIs' distal and proximal outcomes and their tailoring mechanisms, and report their effectiveness. We will also explore studies' considerations of health equity. This will form a comprehensive assessment of JITAIs and their role in promoting health behaviours of AYAs. We will integrate evidence to guide the development and implementation of precise, effective and equitable digital health interventions for AYAs.
Exploring the interplay of psychiatric symptoms, antipsychotic medications, side effects, employment status, and quality of life in Chronic Schizophrenia
Zhou DN, Yang X, Wang W, Jin WQ, Tang YL, Zheng Z and Ren Y
Many factors contribute to quality of life (QoL) in patients with schizophrenia, yet limited research examined these factors in patients in China. This cross-sectional study explores subjective QoL and its associated factors in patients.
A proximity proteomics pipeline with improved reproducibility and throughput
Zhong X, Li Q, Polacco BJ, Patil T, Marley A, Foussard H, Khare P, Vartak R, Xu J, DiBerto JF, Roth BL, Eckhardt M, von Zastrow M, Krogan NJ and Hüttenhain R
Proximity labeling (PL) via biotinylation coupled with mass spectrometry (MS) captures spatial proteomes in cells. Large-scale processing requires a workflow minimizing hands-on time and enhancing quantitative reproducibility. We introduced a scalable PL pipeline integrating automated enrichment of biotinylated proteins in a 96-well plate format. Combining this with optimized quantitative MS based on data-independent acquisition (DIA), we increased sample throughput and improved protein identification and quantification reproducibility. We applied this pipeline to delineate subcellular proteomes across various compartments. Using the 5HT serotonin receptor as a model, we studied temporal changes of proximal interaction networks induced by receptor activation. In addition, we modified the pipeline for reduced sample input to accommodate CRISPR-based gene knockout, assessing dynamics of the 5HT network in response to perturbation of selected interactors. This PL approach is universally applicable to PL proteomics using biotinylation-based PL enzymes, enhancing throughput and reproducibility of standard protocols.
Unraveling unmet needs in ketogenic dietary services: An ERN EpiCARE survey
De Giorgis V, Pasca L, Aznar-Lain G, Bibic I, Bibic V, Darra F, Dianin A, Dressler A, Jonsson H, Komulainen-Ebrahim J, Kverneland M, Molteberg E, Ragona F, de Saint-Martin A, Varesio C, Cross JH and
The implementation and potential of ketogenic dietary therapies (KDTs) have changed over time. The organization of KDT services, the availability of multidisciplinary teams, resources and support for patients and families still vary widely around the world. This diversity is reflected by a lack of consistency in reported outcomes, optimization of using KDT and KDT compliance. To highlight the unmet needs for KDT services, the ERN EpiCARE Ketogenic Dietary Therapy Special Interest Group (KDT SIG) conducted an online survey on KDT implementation and utilization, addressing the following topics: Use and completeness of guidelines and protocols; assessment of compliance and outcome parameters, sustainability and inclusivity in daily life. Consistently reported unmet needs included the lack of psychological support and resources to measure and improve adherence to KDT, the lack of inclusion strategies, and shared guidelines and protocols adapting to specific needs. Future interventions should focus primarily on educational and informative measures together with creation of shared protocols for complex care. PLAIN LANGUAGE SUMMARY: This study provides the results of a survey compiled by clinicians and patients representatives belonging to ERN Epicare, designed to unravel unmet needs from both patients' and healthcare practitioners' perspectives during ketogenic dietary therapies (KDT) provision. Importantly, results show the need to create new shared protocols and guidelines meant for KDT use in complex care situations and to develop future strategies initiatives to support patients improving their social inclusivity.
Participatory research in mental health care services in low- and middle-income countries: a scoping review protocol
Krishnan N, Sunder P, Lalachan N, Mohan M, Venkateswaran C and John D
The objective of this scoping review will be to identify and map the characteristics of participatory research approaches in mental health care services conducted in low- and middle-income countries (LMICs).
Graded Exposure Therapy for Fear Avoidance Behaviour After Concussion (GET FAB): protocol for a multisite Canadian randomised controlled trial
Mikolic A, Klotz T, Brasher P, Yeates K, Vranceanu AM, Kendall KD, Snell DL, Debert CT, Bayley M, Panenka W, Cairncross M, Hunt C, Burke M, Tartaglia MC, Silverberg N and
Persistent symptoms after mild traumatic brain injury (mTBI) negatively affect daily functioning and quality of life. Fear avoidance behaviour, a coping style in which people avoid or escape from activities or situations that they expect will exacerbate their symptoms, maybe a particularly potent and modifiable risk factor for chronic disability after mTBI. This study will evaluate the efficacy of graded exposure therapy (GET) for reducing persistent symptoms following mTBI, with two primary aims: (1) To determine whether GET is more effective than usual care; (2) to identify for whom GET is the most effective treatment option, by evaluating whether baseline fear avoidance moderates differences between GET and an active comparator (prescribed aerobic exercise). Our findings will guide evidence-based care after mTBI and enable better matching of mTBI patients to treatments.
Non-benzodiazepine Hypnotics and Police-Reported Motor Vehicle Crash Risk among Older Adults: A Sequential Target Trial Emulation
Zullo AR, Khan MA, Pfeiffer MR, Margolis SA, Ott BR, Curry AE, Bayer TA, Riester MR and Joyce NR
Non-benzodiazepine hypnotics ( "Z-drugs") are prescribed for insomnia, but might increase risk of motor vehicle crash (MVC) among older adults through prolonged drowsiness and delayed reaction times. We estimated the effect of initiating Z-drug treatment on the 12-week risk of MVC in a sequential target trial emulation. After linking New Jersey driver licensing and police-reported MVC data to Medicare claims, we emulated a new target trial each week (July 1, 2007 - October 7, 2017) in which Medicare fee-for-service beneficiaries were classified as Z-drug-treated or untreated at baseline and followed for an MVC. We used inverse probability of treatment and censoring weighted pooled logistic regression models to estimate risk ratios (RR) and risk differences with 95% bootstrap confidence limits (CLs). There were 257,554 person-trials, of which 103,371 were Z-drug-treated and 154,183 untreated, giving rise to 976 and 1,249 MVCs, respectively. The intention-to-treat RR was 1.06 (95%CLs 0.95, 1.16). For the per-protocol estimand, there were 800 MVCs and 1,241 MVCs among treated and untreated person-trials, respectively, suggesting a reduced MVC risk (RR 0.83 [95%CLs 0.74, 0.92]) with sustained Z-drug treatment. Z-drugs should be prescribed to older patients judiciously but not withheld entirely over concerns about MVC risk.
Psychological and psychosocial interventions for treatment-resistant schizophrenia: a systematic review and network meta-analysis
Salahuddin NH, Schütz A, Pitschel-Walz G, Mayer SF, Chaimani A, Siafis S, Priller J, Leucht S and Bighelli I
Many patients with schizophrenia have symptoms that do not respond to antipsychotics. This condition is called treatment-resistant schizophrenia and has not received specific attention as opposed to general schizophrenia. Psychological and psychosocial interventions as an add-on treatment to pharmacotherapy could be useful, but their role and comparative efficacy to each other and to standard care in this population are not known. We investigated the efficacy, acceptability, and tolerability of psychological and psychosocial interventions for patients with treatment-resistant schizophrenia.
Harnessing health information technology to promote equitable care for patients with limited English proficiency and complex care needs
Strechen I, Wilson P, Eltalhi T, Piche K, Tschida-Reuter D, Howard D, Sutor B, Tiong I, Herasevich S, Pickering B and Barwise A
Patients with language barriers encounter healthcare disparities, which may be alleviated by leveraging interpreter skills to reduce cultural, language, and literacy barriers through improved bidirectional communication. Evidence supports the use of in-person interpreters, especially for interactions involving patients with complex care needs. Unfortunately, due to interpreter shortages and clinician underuse of interpreters, patients with language barriers frequently do not get the language services they need or are entitled to. Health information technologies (HIT), including artificial intelligence (AI), have the potential to streamline processes, prompt clinicians to utilize in-person interpreters, and support prioritization.
A hybrid digital parenting programme to prevent abuse of adolescents in Tanzania: statistical analysis plan for a pragmatic cluster randomised controlled trial
Klapwijk J, Melendez-Torres GJ, Ornellas A, Wambura M, Chetty AN, Baerecke L, Wamoyi J and Cluver LD
Globally, violence against children poses substantial health and economic challenges, with estimated costs nearing USD 7 trillion. This prompts the urgent call for effective evidence-based interventions in preventing and mitigating violence against children. ParentApp is a mobile, open-source application designed to offer a remote version of the Parenting for Lifelong Health (PLH) programme. ParentApp is the first digital parenting intervention for caregivers of adolescents aged 10-17 years to be tested in low- and middle-income settings.
Improving processing speed in adolescents at clinical high risk for psychosis with the Specific COgnitive REmediation plus Surround (SCORES) intervention: Study protocol
Carrión RE, Auther AM, McLaughlin D, John M and Cornblatt BA
Recent preventative approaches with young people at clinical high risk for psychosis (CHR-P) have focused on the remediation of the cognitive deficits that are readily apparent and predictive of future illness. However, the small number of trials using cognitive remediation with CHR-P individuals have reported mixed results. The proposed 2-phased study will test an innovative internet-based and remotely-delivered Specific COgnitive REmediation plus Surround (or SCORES) intervention that targets early processing speed deficits in CHR-P adolescents aged 14-20 years old.
Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, placebo-controlled and delayed-start, neuroimaging trial in depression
Poulin JM, Bigford GE, Lanctôt KL, Giacobbe P, Schaffer A, Sinyor M, Rabin JS, Masellis M, Singnurkar A, Pople CB, Lipsman N, Husain MI, Rosenblat JD, Cao X, MacIntosh BJ and Nestor SM
Major depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin's acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression.
A world-wide study on delirium assessments and presence of protocols
Nydahl P, Liu K, Bellelli G, Benbenishty J, van den Boogaard M, Caplan G, Chung CR, Elhadi M, Gurjar M, Heras-La Calle G, Hoffmann M, Jeitziner MM, Krewulak K, Mailhot T, Morandi A, Nawa RK, Oh ES, Collet MO, Paulino MC, Lindroth H, von Haken R and
Delirium is a common complication of older people in hospitals, rehabilitation and long-term facilities.
The EQ-5D-5L valuation study for Trinidad and Tobago
Bailey H, Jonker MF, Pullenayegum E, Rencz F and Roudijk B
The 2016 EQ-5D-3L value set for Trinidad and Tobago (T&T) allows for the calculation of EQ-5D-5L values via the crosswalk algorithm. The 2016 value set was based on methods predating the EQ-VT protocol, now considered the gold standard for developing EQ-5D value sets. Furthermore, direct elicitation of EQ-5D-5L is preferred over crosswalked values. This study aimed to produce an EQ-5D-5L value set for T&T.
Developing inclusive public involvement and engagement activities with secondary school students and educational professionals: a protocol
Cross L, Banham D, Melendez-Torres GJ, Ford T, van Sluijs E and Liabo K
Public involvement and engagement (PI&E) is increasingly recognised as an important component of research. It can offer valuable insights from those with experiential knowledge to improve research quality, relevance, and reach. Similarly, schools are ever more common sites for health research and, more recently, PI&E. However, 'gold-standard' practice is yet to be established, and activities/approaches remain underreported. As a result, knowledge can remain localised or lost. Diversity and inclusion also remains a challenge.
Incident diabetes in adolescents using antidepressant: a systematic review and meta-analysis
Movahed F, Heidari E, Sadeghi D, Rezaei Nejad A, Abyaneh R, Zarei M, Beigi F, Abdollahi A and Shafiee A
The use of antidepressants has been on the rise among adolescents and young adults, populations also increasingly at risk for type 2 diabetes. However, the relationship between antidepressant uses and diabetes incidence in these age groups remains poorly understood.
Sequenced treatment effectiveness for posttraumatic stress (STEPS) trial: A protocol for a pragmatic comparative effectiveness trial with baseline results
Fortney JC, Kaysen DL, Engel CC, Cerimele JM, Nolan JP, Chase E, Blanchard BE, Hauge S, Bechtel J, Moore DL, Taylor A, Acierno R, Nagel N, Sripada RK, Painter JT, DeBeer BB, Bluett E, Teo AR, Morland LA and Heagerty PJ
There have only been two efficacy trials reporting a head-to-head comparison of medications and psychotherapy for posttraumatic stress disorder (PTSD), and neither was conducted in primary care. Therefore, in this pragmatic trial we compare outcomes of primary care patients randomized to initially receive a brief trauma-focused psychotherapy or a choice of three antidepressants. In addition, because there are few trials examining the effectiveness of subsequent treatments for patients not responding to the initial treatment, we also compare the outcomes of those switching or augmenting treatments.
Delirium in the US: Results from 2023 cross-sectional World Delirium Awareness Day prevalence study
Lindroth H, Byrnes T, Fuchita M, Hetland B, Liu K, Maya K, McAndrew NS, Mulkey MA, Nydahl P, Palakshappa J, von Haken R, Psoter KJ, Oh ES and
Delirium is an acute brain dysfunction associated with an increased risk of mortality and future dementia.
State of the Science: Evidence-based treatments for posttraumatic stress disorder delivered via telehealth
Bruce MJ, Pagán AF and Acierno R
Psychotherapy delivered via telehealth technology is not an artifact of the COVID-19 pandemic. Indeed, widespread, telehealth-delivered, evidence-based psychotherapy preceded the pandemic, as did randomized controlled noninferiority trials supporting this modality. It is, thus, not difficult to predict that telehealth will be an integral part of daily clinical life moving forward. With respect to posttraumatic stress disorder (PTSD) specifically, there is a substantial number of studies on the feasibility, acceptability, and effectiveness of evidence-based treatments provided via videoconferencing. In this review, we delineate the literature establishing strong support for remote delivery of prolonged exposure (PE) and cognitive processing therapy (CPT); there is also promising support for written exposure therapy (WET) and trauma-focused cognitive behavioral therapy (TF-CBT). We also mention adjunctive and integrative modifications to better serve patients with PTSD. One such intervention, behavioral activation and therapeutic exposure (BATE), has several studies supporting telehealth delivery, whereas concurrent treatment of PTSD and substance use disorders using the PE protocol (COPE) and cognitive behavioral therapy for insomnia (CBT-I) would benefit from further research. Integrating instrumental peer support into telehealth-delivered PE shows promise in retaining patients in treatment. Finally, we provide ideas to maximize telehealth delivery effectiveness, explore future research directions, and discuss ways to advocate for the expansion of telehealth services from an equity perspective.
Insights into interoceptive and emotional processing: Lessons from studies on insular HD-tDCS
Kipping M, Mai-Lippold SA, Herbert BM, Desdentado L, Kammer T and Pollatos O
Interoception, the processing of internal bodily signals, is proposed as the fundamental mechanism underlying emotional experiences. Interoceptive and emotional processing appear distorted in psychiatric disorders. However, our understanding of the neural structures involved in both processes remains limited. To explore the feasibility of enhancing interoception and emotion, we conducted two studies using high-definition transcranial direct current stimulation (HD-tDCS) applied to the right anterior insula. In study one, we compared the effects of anodal HD-tDCS and sham tDCS on interoceptive abilities (sensibility, confidence, accuracy, emotional evaluation) in 52 healthy subjects. Study two additionally included physical activation through ergometer cycling at the beginning of HD-tDCS and examined changes in interoceptive and emotional processing in 39 healthy adults. In both studies, HD-tDCS was applied in a single-blind cross-over online design with two separate sessions. Study one yielded no significant effects of HD-tDCS on interoceptive dimensions. In study two, significant improvements in interoceptive sensibility and confidence were observed over time with physical preactivation, while no differential effects were found between sham and insula stimulation. The expected enhancement of interoceptive and emotional processing following insula stimulation was not observed. We conclude that HD-tDCS targeting the insula does not consistently increase interoceptive or emotional variables. The observed increase in interoceptive sensibility may be attributed to the activation of the interoceptive network through physical activity or training effects. Future research on HD-tDCS involving interoceptive network structures could benefit from protocols targeting larger regions within the network, rather than focusing solely on insula stimulation.
Measuring Sleep and Activity Patterns in Adult Zebrafish
Doldur-Balli F, Zimmerman AJ, Seiler C, Veatch O and Pack AI
Sleep is an essential behavior that is still poorly understood. Sleep abnormalities accompany a variety of psychiatric and neurological disorders, and sleep can serve as a modifiable behavior in the treatment of these disorders. Zebrafish () has proven to be a powerful model organism to study sleep and the interplay between sleep and these disorders due to the high conservation of the neuro-modulatory mechanisms that control sleep and wake states between zebrafish and humans. The zebrafish is a diurnal vertebrate with a relatively simple nervous system compared to mammalian models, exhibiting conservation of sleep ontogeny across different life stages. Zebrafish larvae are an established high-throughput model to assess sleep phenotypes and the biological underpinnings of sleep disturbances. To date, sleep measurement in juvenile and adult zebrafish has not been performed in a standardized and reproducible manner because of the relatively low-throughput nature in relation to their larval counterparts. This has left a gap in understanding sleep across later stages of life that are relevant to many psychiatric and neurodegenerative disorders. Several research groups have used homemade systems to address this gap. Here, we report employing commercially available equipment to track activity and sleep/wake patterns in juvenile and adult zebrafish. The equipment allows researchers to perform automated behavior assays in an isolated environment with light/dark and temperature control for multiple days. We first explain the experimental procedure to track the sleep and activity of adult zebrafish and then validate the protocol by measuring the effects of melatonin and DMSO administration. Key features • Allows an isolated and controllable environment to carry out activity and sleep assays in juvenile and adult zebrafish. • Measures activity of zebrafish in life stages later than early development, which requires feeding animals during the assay. • Requires use of a commercially available equipment system and six tanks. • The activity of zebrafish can be tracked for five days including an acclimation step.
Experiences of telehealth during and after the COVID-19 pandemic and preferences for future care of people with systemic sclerosis: a cross-sectional study
Nassar EL, Virgili-Gervais G, Carrier ME, Kwakkenbos L, Henry RS, Hu S, Provencher S, Golberg M, Bartlett SJ, Mouthon L, Patten SB, Varga J, Benedetti A, Thombs BD and
Study Protocol for Pain Self-Management and Patient-Oriented Buprenorphine Dosing for Pain and Retention in Office-Based Opioid Treatment: A Hybrid Type 1, 2 × 2 Factorial Randomized Controlled Trial
Salay M, Edwards KA, Winstanley EL, Bachrach RL, Bulls HW, Hanmer J, Liebschutz JM, Robbins J, Wilson JD, Yu L, Merlin JS and Murray-Krezan C
Chronic pain is a significant factor for patients with opioid use disorder (OUD) contributing to suboptimal retention in buprenorphine treatment, which is a crucial predictor of long-term health outcomes. This study aims to address the critical need for effective interventions targeting chronic pain management within office-based opioid treatment (OBOT) programs. We are conducting a multisite, hybrid type 1, 2 × 2 factorial randomized clinical trial to determine the effectiveness of 2 novel interventions, pain self-management (PSM) and patient-oriented buprenorphine dosing (POD), to decrease pain interference and improve retention in buprenorphine treatment. PSM, a manualized and customizable approach delivered through individual and peer-led group sessions, aims to decrease pain-related symptoms and quality of life. POD involves split dosing of buprenorphine to extend the duration of analgesia to better match its duration of efficacy at managing OUD symptoms, leading to improved retention in buprenorphine treatment. Eligible participants will be randomized into 1 of 4 groups: (1) PSM + POD, (2) PSM + Standard Buprenorphine Dosing, (3) Usual Care + POD, or (4) Usual Care + Standard Buprenorphine Dosing. Usual Care refers to usual care for chronic pain and Standard Buprenorphine Dosing refers to the participant's current dosing regimen. Secondary objectives encompass overall pain reduction, decreased opioid use, improved pain symptom management, and exploration of implementation strategies. The supplemental approved protocol provides comprehensive insights into the procedures and variables being investigated. As part of the HEAL Initiative-funded Integrative Management of Chronic Pain and OUD for Whole Recovery (IMPOWR) network, this study aims to fill gaps in behavioral and medication treatments for individuals with co-occurring chronic pain and OUDs, improving pain management and retention in care. Successful outcomes from this trial may inform future larger trials, offering essential evidence for implementation considerations and reimbursement decisions.
Study protocol for a single-blind, parallel-group, randomized, controlled superiority trial of intensive versus weekly delivered prolonged exposure for adults with post-traumatic stress disorder
Bragesjö M, Fina B, Ivanova E, Ivanov VZ and Rück C
Prolonged exposure (PE) therapy is widely recognized as an effective treatment for post-traumatic stress disorder (PTSD) and is often considered one of the primary options for addressing this condition. Nevertheless, a significant proportion of patients (30-51%) fail to demonstrate clinically significant symptom changes. One of the reasons is that a high proportion of patients drop out from treatment, which often lasts for a minimum of 3-4 months. Hence, there is an urgent need for PTSD treatments that can be delivered to decrease dropout rates. A more intensive PE treatment approach has been suggested to decrease dropout rates and in addition achieve faster recovery rates and has shown promising effects on reducing PTSD symptoms but needs to be tested against firsthand treatment.
A phase 3 randomised double-blind placebo-controlled trial of mirtazapine as a pharmacotherapy for methamphetamine use disorder: a study protocol for the Tina Trial
McKetin R, Degan TJ, Saunders L, Nguyen L, Dore G, Shoptaw S, Farrell M, Degenhardt L, Kelly PJ, Turner A, Clare PJ, Dean OM, Arunogiri S, Colledge-Frisby S, Koeijers J, Goodman-Meza D, Sinclair B, Reid D, Hill H, Hayllar J, Christmass M, Cordaro F, Lundin R, Liaw W, Liu D, Holyoak E, Wu BT, Keygan J, Kontogiannis A, Palmer L, Morrison C, Wrobel A, Hyland B, Byrne M, Russell S, Zahra E and Berk M
There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder.
Commentary With Study Protocol: Implementation and Effectiveness of Mindfulness-Oriented Recovery Enhancement (MORE) as an Adjunct to Methadone Treatment for Opioid Use Disorder (IMPOWR-MORE)
Cooperman NA, Shen J, Gordon AJ and Garland EL
Traditional methadone treatment (MT) for opioid use disorder (OUD) fails to systematically address the physical pain, emotion dysregulation, and reward processing deficits that co-occur with OUD, and novel interventions that address these issues are needed to improve MT outcomes. Mindfulness-Oriented Recovery Enhancement (MORE) remediates the hedonic dysregulation in brain reward systems that is associated with OUD. Our pilot and phase 2 randomized controlled trials of MORE were the first to demonstrate MORE's feasibility, acceptability, and efficacy as delivered in MT clinics; MORE significantly reduced drug use (eg, benzodiazepines, barbiturates, cocaine, marijuana, opioids, and other drugs), craving, depression, anxiety, and pain among people with OUD. However, uptake of novel, efficacious interventions like MORE may be slow in MT because time and resources are often limited. Therefore, to best address potential implementation issues and to optimize future MORE implementation and dissemination, in this study, we will utilize a Type 2, Hybrid Implementation-Effectiveness study design. We will not only evaluate MORE's effectiveness but also assess barriers and facilitators to integrating MORE into MT. MT clinicians will receive training in (1) a higher intensity MORE implementation strategy consisting of training in the full MORE treatment manual or (2) a minimal intensity implementation strategy consisting of a simple, scripted mindfulness practice (SMP) extracted from the MORE treatment manual with minimal training. We aim to: (1) using a Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, examine barriers and facilitators to implementation of MORE and SMP in MT, and evaluate strategies for optimizing training, fidelity, and engagement, (2) optimize existing MORE and SMP training and implementation toolkits, including adaptable resources that can accelerate the translation of evidence into practice, and (3) compared to usual MT, evaluate the relative effectiveness of MORE plus MT or SMP plus MT (N = 450).
Shared symptomatology between atopic dermatitis, ADHD and autism spectrum disorder: a protocol for a systematic scoping review
Nguyen NT, Ragamin A, Rietman AB, Nijsten TEC and Schappin R
Children with atopic dermatitis (AD) are more at risk for the neurodevelopmental disorders attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) with parallel increases in global prevalences. Children afflicted with these conditions appear to share similar problems in sensory modulation but investigational studies on the underlying aetiology are scarce. This scoping review aims to find knowledge gaps, collate hypotheses and to summarise available evidence on the shared pathophysiology of AD, ADHD and ASD in children.
Heart rate vARiability and physical activity in inpatient treatMent of burnOut and DepressIon (HARMODI): protocol of a cross-sectional study with up to 8-week follow up
Turner W, Brühl A, Böker H, Schulze B, Marschall K, La Marca R, Pfaff M, Russmann T and Schmidt-Trucksäss A
Chronic stress can cause an imbalance within the autonomic nervous system, thereby affecting cardiovascular and mental health. Physical activity (PA) may have a positive effect on the autonomic nervous system and stress-related disorders, such as depression and burnout. Heart rate variability (HRV) is a non-invasive marker of the autonomic nervous system. However, limited and inconsistent data exist on the exact relationship between HRV, PA and depression and burnout symptoms. The HARMODI study aims to explore whether HRV is a feasible marker of depression and burnout symptoms and aims to evaluate the role of PA in the treatment of stress-related disorders.
Clinical effectiveness and cost-effectiveness of Structured Psychological Support for people with probable personality disorder in mental health services in England: study protocol for a randomised controlled trial
Crawford MJ, Leeson VC, Evans R, Goulden N, Weaver T, Trumm A, Barrett BM, Khun-Thompson F, Pandya SP, Saunders KE, Lamph G, Woods D, Smith H, Greenall T, Nicklin V and Barnicot K
Evidence-based psychological treatments for people with personality disorder usually involve attending group-based sessions over many months. Low-intensity psychological interventions of less than 6 months duration have been developed, but their clinical effectiveness and cost-effectiveness are unclear.
Digital cognitive-behavioural therapy application compared with zolpidem for the treatment of insomnia: protocol for an exploratory randomised controlled trial
Shimizu E, Sato D, Hirano Y, Ebisu H, Kagayama Y and Hanaoka H
Insomnia is a common health problem and cognitive-behavioural therapy (CBT) is recommended as a treatment. As there is a critical shortage of CBT-trained therapists, we developed a digital CBT application (IIIP MED: Sleepy Med) as Software as a Medical Device for insomnia. This paper describes the study protocol for an exploratory randomised controlled trial (RCT) to evaluate effectiveness and safety of our developed digital CBT (dCBT) for 5 weeks compared with zolpidem tartrate for patients with insomnia disorder.
Alterations in Neurotrophins in Alcohol-Addicted Patients during Alcohol Withdrawal
Malewska-Kasprzak M, Skibińska M and Dmitrzak-Węglarz M
Alcohol use disorder (AUD) is related to mental and somatic disorders that result in alcohol withdrawal syndrome (AWS), with 30% of AWS cases leading to life-threatening delirium tremens (DTs). Currently, studies do not support using any one biomarker in DTs. Neurotrophins affect neuromodulation, playing a role in the pathogenesis of AUD, AWS, and DTs.
Study protocol on the efficacy of exergames-acceptance and commitment therapy program for the treatment of major depressive disorder: comparison with acceptance and commitment therapy alone and treatment-as-usual in a multicentre randomised controlled trial
Zhang B, Deng H, Ren J, Legrand FD, Ahmad Yusof H, Zhang R and Leong Bin Abdullah MFI
The prevalence of major depressive disorder (MDD) is on the rise globally, and the use of antidepressant medications for its treatment does not usually result in full remission. However, the combination of physical exercise and psychotherapy for the treatment of MDD increase the rate of full remission among patients. This three-armed, parallel-group, double-blinded randomised controlled trial (RCT) aims to assess and compare the effects between the combination of exergame and acceptance and commitment therapy (e-ACT) programme, ACT only and treatment-as-usual (TAU) control groups on the severity of depression and anxiety symptoms, the degree of experiential avoidance and quality of life (QoL) and the serum levels of depression biomarkers (such as brain-derived neurotrophic factor, C-reactive protein and vascular endothelial growth factor) among patients with MDD across three time points.
Examining cognitive behavioral therapy interventions for unaccompanied minors: a systematic review and qualitative research synthesis
Morroni D, Konstantinou P, Gkleka C, Kassianos AP and Karekla M
This systematic review examined the evidence on effectiveness and acceptability of cognitive behavioral therapy (CBT) interventions in improving quality of life (QoL) and psychological well-being of unaccompanied minors (UM).
Temporal-Posterior Alpha Power in Resting-State Electroencephalography as a Potential Marker of Complex Childhood Trauma in Institutionalized Adolescents
Marcu GM, Băcilă CI and Zăgrean AM
The present study explored whether, given the association of temporal alpha with fear circuitry (learning and conditioning), exposure to complex childhood trauma (CCT) is reflected in the temporal-posterior alpha power in resting-state electroencephalography (EEG) in complex trauma-exposed adolescents in a sample of 25 adolescents and similar controls aged 12-17 years. Both trauma and psychopathology were screened or assessed, and resting-state EEG was recorded following a preregistered protocol for data collection. Temporal-posterior alpha power, corresponding to the T5 and T6 electrode locations (international 10-20 system), was extracted from resting-state EEG in both eyes-open and eyes-closed conditions. We found that in the eyes-open condition, temporal-posterior alpha was significantly lower in adolescents exposed to CCT relative to healthy controls, suggesting that childhood trauma exposure may have a measurable impact on alpha oscillatory patterns. Our study highlights the importance of considering potential neural markers, such as temporal-posterior alpha power, to understanding the long-term consequences of CCT exposure in developmental samples, with possible important clinical implications in guiding neuroregulation interventions.
Effects of cognitive behavioural therapy and exposure-response prevention on brain activation in obsessive-compulsive disorder patients: systematic review and meta-analysis
Stephenson C, Philipp-Muller A, Moghimi E, Nashed JY, Cook DJ, Shirazi A, Milev R and Alavi N
Current psychotherapeutic treatments for OCD, while effective, have complex outcomes with mixed efficacy. Previous research has observed baseline brain activation patterns in OCD patients, elucidating some of the implications of this disorder. Observing the effects of evidence-based psychotherapeutics for OCD on brain activation (through MRI) may provide a more comprehensive outline of pathology. This systematic review and meta-analysis evaluated the effects of cognitive behavioural therapy (CBT) with exposure-response prevention (ERP) on brain activation in OCD patients. Academic databases were systematically searched, and the outcomes evaluated included changes in brain activation and symptom severity between baseline and post-treatment. Patients (n = 193) had confirmed OCD diagnosis and underwent protocolized CBT with ERP programs delivered by trained therapists. Participants in the CBT with ERP programs demonstrated significant improvements in symptom severity (Cohen's d = - 1.91). In general, CBT with ERP resulted in decreased activation post-treatment in the frontal (Cohen's d = 0.40), parietal (Cohen's d = 0.79), temporal (Cohen's d = 1.02), and occipital lobe (Cohen's d = 0.76), and cerebellum (Cohen's d = - 0.78). The findings support CBT with ERP's ability to improve brain activation abnormalities in OCD patients. By identifying regions that improved activation levels, psychotherapy programs may benefit from the addition of function-specific features that could improve treatment outcomes.
A qualitative meta-synthesis of service users' and carers' experiences of assessment and involuntary hospital admissions under mental health legislations: a five-year update
Bartl G, Stuart R, Ahmed N, Saunders K, Loizou S, Brady G, Gray H, Grundy A, Jeynes T, Nyikavaranda P, Persaud K, Raad A, Foye U, Simpson A, Johnson S and Lloyd-Evans B
Compulsory admissions occur in psychiatric hospitals around the world. They result in coercive and sometimes traumatic experiences for service users and carers. Legal and service reforms in various countries are intended to reduce rates of detention and improve service user experience. We aimed to inform policy and service delivery by providing an up-to-date synthesis of qualitative evidence on service users' and carers' experiences of assessment and detention under mental health legislation, updating previous reviews in which we searched for literature published up to 2018.
Comparing times of self-harm presentations to hospital emergency departments in children, adolescents, young adults and adults: a national registry study 2007-2019
McEvoy D, Joyce M, Mongan D, Clarke M and Codd M
The few studies that have explored self-harm presentation times at hospital emergency departments (EDs) - an important factor that can determine if a patient receives a mental health assessment - primarily focus on adult samples. This study examined the times of self-harm presentations to EDs, self-harm methods used, mental health assessments, and admission data across different age-groups.
Transcranial direct current stimulation improves heart rate variability: A systematic review and meta-analysis
Ko DK, Lee H, Kim DI, Park YM and Kang N
Heart rate variability (HRV) is a useful tool for evaluating cardiovascular autonomic nervous system (ANS) functions. This systematic review and meta-analysis examined the potential effects of transcranial direct current stimulation (tDCS) protocols on HRV parameters.
Protocol for the development of a tool to map systemic sclerosis pain sources, patterns, and management experiences: a Scleroderma Patient-centered Intervention Network patient-researcher partnership
Dal Santo T, Golberg M, Nassar EL, Carrier ME, Hu S, Kwakkenbos L, Bartlett SJ, Fox RS, Lee YC, Varga J, Benedetti A, Thombs BD and
Systemic sclerosis (SSc) is a rare, complex autoimmune rheumatic disease with multiple factors that contribute to pain. People with SSc emphasize the effect pain has on their quality of life, but no studies have systematically examined the frequency and relative importance of different SSc pain sources, patterns of pain from different sources, and pain management experiences. Our objectives are to (1) develop a tool, jointly with researchers, health care providers, and patients, to map sources of pain in SSc, determine patterns of pain from different sources, and understand pain management experiences; and (2) administer the final tool version to participants in the large multinational Scleroderma Patient-centered Intervention Network (SPIN) Cohort.
Road safety implications of the partial legalisation of cannabis in Germany: protocol for a quasi-experimental study
Schranz A, Verthein U and Manthey J
Germany is reforming its legal approach to cannabis, allowing the possession and cultivation of cannabis for recreational purposes. The objective of this study is to investigate the impact of the policy reform on (1) The prevalence of cannabis use in the general population and (2) Driving under the influence of cannabis (DUIC) among regular users.
Efficacy and Safety of Esmethadone (REL-1017) in Patients With Major Depressive Disorder and Inadequate Response to Standard Antidepressants: A Phase 3 Randomized Controlled Trial
Fava M, Stahl SM, Pani L, De Martin S, Cutler AJ, Maletic V, Gorodetzky CW, Vocci FJ, Sapienza FL, Kosten TR, Kröger C, Champasa P, O'Gorman C, Guidetti C, Alimonti A, Comai S, Mattarei A, Folli F, Bushnell D, Traversa S, Inturrisi CE, Manfredi PL and Pappagallo M
To test esmethadone (REL-1017) as adjunctive treatment in patients with major depressive disorder (MDD) and inadequate response to standard antidepressants. In this phase 3, double-blind, placebo-controlled trial, outpatients with MDD () were randomized to daily oral esmethadone (75 mg on day 1, followed by 25 mg daily on days 2 through 28) or placebo between December 2020 and December 2022. The primary efficacy measure was change from baseline (CFB) to day 28 in the Montgomery-Asberg Depression Rating Scale (MADRS) score. The intent-to-treat (ITT) population included all randomized participants. The per-protocol (PP) population included completers without major protocol deviations impacting assessment. Post hoc analyses included participants with severe depression (baseline MADRS score ≥35). For the ITT analysis (n = 227), mean CFB was 15.1 (SD 11.3) for esmethadone (n = 113) and 12.9 (SD 10.4) for placebo (n = 114), with a mean difference (MD) of 2.3, which was not statistically significant ( = .154; Cohen effect size [ES] = 0.21). Remission rates were 22.1% and 13.2% ( = .076), and response rates were 39.8% and 27.2% ( = .044) with esmethadone and placebo, respectively. For the PP analysis (n = 198), mean CFB was 15.6 (SD 11.2) for esmethadone (n = 101) and 12.5 (SD 9.9) for placebo (n = 97), with an MD of 3.1 ( = .051; ES =0.29). In post hoc analyses of patients with baseline MADRS ≥35 in the ITT population (n = 112), MD was 6.9; = .0059; ES = 0.57, and for the PP population (n = 98), MD was 7.9; = .0015; ES = 0.69. Adverse events (AEs) were predominantly mild or moderate and transient, with no significant differences between groups. The primary end point was not met. Esmethadone showed stronger efficacy in PP than in ITT analyses, with the discrepancy not attributable to AEs impacting treatment adherence. Significant efficacy occurred in post hoc analyses of patients with severe depression. Esmethadone was well tolerated, consistent with prior studies. ClinicalTrials.gov identifier: NCT04688164.
Treatment expectations and clinical outcomes following repetitive transcranial magnetic stimulation for treatment-resistant depression
Mollica A, Ng E, Burke MJ, Nestor SM, Lee H, Rabin JS, Hamani C, Lipsman N and Giacobbe P
Patient expectations, including both positive (placebo) and negative (nocebo) effects, influence treatment outcomes, yet their impact on acute repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) is unclear.
Protocol-based assessment and management of first episode psychosis: Comparison of short and medium-term outcomes in psychopathology, quality of life, functioning and family burden across two sites in India
Chadda RK, Sood M, Chawla N, Padmavati R, Thara R, Raghavan V, Shukla T, Patil V, Sen MS, Mohan M, Iyer S, Shah J, Madan J, Birchwood M, Meyer C, Lilford RJ, Furtado V, Currie G and Singh SP
Standard assessment and management protocols exist for first episode psychosis (FEP) in high income countries. Due to cultural and resource differences, these need to be modified for application in low-and middle-income countries.
Strategies, processes, outcomes, and costs of implementing experience sampling-based monitoring in routine mental health care in four European countries: study protocol for the IMMERSE effectiveness-implementation study
Reininghaus U, Schwannauer M, Barne I, Beames JR, Bonnier RA, Brenner M, Breznoščáková D, Dančík D, De Allegri M, Di Folco S, Durstewitz D, Gugel J, Hajdúk M, Heretik A, Izáková Ľ, Katreniakova Z, Kiekens G, Koppe G, Kurilla A, Marelli L, Nagyova I, Nguyen H, Pečeňák J, Schulte-Strathaus JCC, Sotomayor-Enriquez K, Uyttebroek L, Weermeijer J, Wolters M, Wensing M, Boehnke JR, Myin-Germeys I and Schick A
Recent years have seen a growing interest in the use of digital tools for delivering person-centred mental health care. Experience Sampling Methodology (ESM), a structured diary technique for capturing moment-to-moment variation in experience and behaviour in service users' daily life, reflects a particularly promising avenue for implementing a person-centred approach. While there is evidence on the effectiveness of ESM-based monitoring, uptake in routine mental health care remains limited. The overarching aim of this hybrid effectiveness-implementation study is to investigate, in detail, reach, effectiveness, adoption, implementation, and maintenance as well as contextual factors, processes, and costs of implementing ESM-based monitoring, reporting, and feedback into routine mental health care in four European countries (i.e., Belgium, Germany, Scotland, Slovakia).
The dose-dependent effect of the D2R agonist quinpirole microinjected into the ventral pallidum on information flow in the limbic system
Peczely L and Grace AA
The ventral pallidum (VP) receives its primary inputs from the nucleus accumbens (NAC) and the basolateral amygdala (BLA). We demonstrated recently that in the VP, the D2 DA receptor (DR) agonist quinpirole dose-dependently facilitates memory consolidation in inhibitory avoidance and spatial learning. In the VP, DR can be found both on NAC and BLA terminals. According to our hypothesis, quinpirole microinjected into the VP can facilitate memory consolidation via modulation of synaptic plasticity on NAC and/or BLA terminals. The effect of intra-VP quinpirole on BLA-VP and NAC shell-VP synapses was investigated via a high frequency stimulation (HFS) protocol. Quinpirole was administered in three doses into the VP of male Sprague-Dawley rats after HFS; controls received vehicle. To examine whether an interaction between the NAC shell and the BLA at the level of the VP was involved, tetrodotoxin (TTX) was microinjected into one of the nuclei while stimulating the other nucleus. Our results showed that quinpirole dose-dependently modulates BLA-VP and NAC shell-VP synapses, similar to those observed in inhibitory avoidance and spatial learning, respectively. The lower dose inhibits BLA inputs, while the larger doses facilitates NAC shell inputs. The experiments with TTX demonstrates that the two nuclei do not influence each others' evoked responses in the VP. Power spectral density analysis demonstrated that independent from the synaptic facilitation, intra-VP quinpirole increases the amplitude of gamma frequency band after NAC HFS, and BLA tonically suppresses the NAC's HFS-induced gamma facilitation. In contrast, HFS of the BLA results in a delayed, transient increase in the amplitude of the gamma frequency band correlating with the LTP of the P1 component of the VP response to BLA stimulation. Furthermore, our results demonstrate that the BLA plays a prominent role in the generation of the delta oscillations: HFS of the BLA leads to a gradually increasing delta frequency band facilitation over time, while BLA inhibition blocks the NAC's HFS induced strong delta facilitation. These findings demonstrate that there is a complex interaction between the NAC shell region and the VP, as well as the BLA and the VP, and support the important role of VP DRs in the regulation of limbic information flow.
Study protocol for the Treating Opioid Patients' Pain and Sadness (TOPPS) study - A randomized control trial to lower depression and chronic pain interference, and increase care retention among persons receiving buprenorphine
Stein MD, Bendiks S, Karzhevsky S, Pierce C, Dunn A, Majeski A, Herman DS and Weisberg RB
Persons receiving prescription buprenorphine for opioid use disorder experience high rates of comorbid conditions such as chronic pain and depression, which present barriers to buprenorphine care retention. This paper describes the protocol of the TOPPS (Treating Opioid Patients' Pain and Sadness) study, which compares a values-based, behavioral activation intervention with a health education contact-control condition, with the aim of decreasing chronic pain and depression, and increasing buprenorphine care retention for persons with opioid use disorder.
The TOTAL trial for weight management participation: A randomized controlled trial protocol
Funk LM, Williams CB, Breuer CR, Hetzel S, LaSage SC, Villasenor CJ, Moin T, Cook J, Sampene E, Stroupe KT, Alagoz E, Raffa SD and Voils CI
The three types of evidence-based treatment options for adults with overweight and obesity - behavioral weight management, anti-obesity medications (AOM), and bariatric surgery - are underutilized in the Veterans Health Administration (VHA) system. Our objective in this manuscript is to describe the study protocol for an adequately powered randomized controlled trial (RCT) of a behavioral intervention: TOTAL (Teaching Obesity Treatment Options to Adult Learners) to increase patient uptake of obesity treatment.
Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression: A Secondary Analysis of a Randomized Clinical Trial
Jha MK, Wilkinson ST, Krishnan K, Collins KA, Sanacora G, Murrough J, Goes F, Altinay M, Aloysi A, Asghar-Ali A, Barnett B, Chang L, Costi S, Malone D, Nikayin S, Nissen SE, Ostroff R, Reti I, Wolski K, Wang D, Hu B, Mathew SJ and Anand A
The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD.
Ketamine treatment for anhedonia in unipolar and bipolar depression: a systematic review
Kwaśny A, Kwaśna J, Wilkowska A, Szarmach J, Słupski J, Włodarczyk A and Cubała WJ
Ketamine, an N-methyl-D-aspartate receptor antagonist, is a racemic mixture of esketamine and arketamine used to treat unipolar and bipolar depression. Preliminary reports indicate that it may be beneficial for depressed patients reporting symptoms of anhedonia. In this systematic review we aim to assess and analyze the existing body of evidence regarding the therapeutic effects of ketamine on the domain of anhedonia. Electronic databases (PubMed, APA Psycinfo and Web of Science) were searched from inception to November 2023. Protocol was registered in PROSPERO under the identifier CRD42023476603. A total of twenty-two studies, including four randomized-controlled trials and eighteen open-label trials were included. All studies reported alleviation of anhedonia symptoms following ketamine or esketamine administration, regardless of the number of infusions. Several important limitations were included, first and foremost low number of placebo-controlled randomized-controlled trials. This review indicates a potential anti-anhedonic effect of ketamine in patients with depression. Several trials used neuroimaging techniques which confirm ketamine's effect on functional connectivity correlating with the improvement in anhedonia. Despite considerable variations in methodology and the specific brain regions investigated, these studies collectively point towards ketamine's neuroplastic effects in mitigating anhedonia.
Protocol for a double-blind placebo-controlled randomised controlled trial assessing the impact of oral semaglutide in amyloid positivity (ISAP) in community dwelling UK adults
Koychev I, Adler AI, Edison P, Tom B, Milton JE, Butchart J, Hampshire A, Marshall C, Coulthard E, Zetterberg H, Hellyer P, Cormack F, Underwood BR, Mummery CJ and Holman RR
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), currently marketed for type 2 diabetes and obesity, may offer novel mechanisms to delay or prevent neurotoxicity associated with Alzheimer's disease (AD). The impact of semaglutide in amyloid positivity (ISAP) trial is investigating whether the GLP-1 RA semaglutide reduces accumulation in the brain of cortical tau protein and neuroinflammation in individuals with preclinical/prodromal AD.
Reducing intersectional stigma among transgender women in Brazil to promote uptake of HIV testing and PrEP: study protocol for a randomised controlled trial of Manas por Manas
Sevelius J, Veras MASM, Gomez JL, Saggese G, Mocello AR, Bassichetto KC, Neilands TB and Lippman SA
Globally, transgender ('trans') women experience extreme social and economic marginalisation due to intersectional stigma, defined as the confluence of stigma that results from the intersection of social identities and positions among those who are oppressed multiple times. Among trans women, gender-based stigma intersects with social positions such as engagement in sex work and substance use, as well as race-based stigma to generate a social context of vulnerability and increased risk of HIV acquisition. In Brazil, trans women are the 'most at-risk' group for HIV, with 55 times higher estimated odds of HIV infection than the general population; further, uptake of HIV testing and pre-exposure prophylaxis (PrEP) among trans women is significantly lower than other at-risk groups. Through extensive formative work, we developed Manas por Manas, a multilevel intervention using HIV prevention strategies with demonstrated feasibility and acceptability by trans women in Brazil, to address intersectional stigma and increase engagement in the HIV prevention continuum.
Training and supervision of physical health professionals to implement mental health care in paediatric epilepsy clinics
Coughtrey AE, Bennett SD, Stanick C, Chorpita B, Dalrymple E, Fonagy P, Helen Cross J, Ford T, Heyman I, Moss-Morris R, and Shafran R
Children and young people with epilepsy are more likely to experience multiple mental health problems than those without chronic physical health conditions, yet they often do not receive evidence-based (or indeed any) psychological interventions. Integrated healthcare is recommended as a solution to address these inequalities, but remains limited in the United Kingdom. This is partly due to the lack of training and availability of ongoing supervision for clinicians to ensure the safe and effective delivery of treatments. This study aimed to train and provide supervision for health professionals to deliver a modular cognitive-behavioural intervention for common mental health problems, optimised for use in paediatric epilepsy. Specifically, this study aimed to measure therapist competence and evaluate the acceptability of training and supervision.
PRECISE trial (Pain RElief Combination Intervention StratEgies): protocol for the clinical trial of a pregabalin-melatonin combination for fibromyalgia
Gilron I, DeBow C, Elkerdawy H, Khan JS, Salomons TV, Duggan S, Tu D, Holden RR, Milev R, Buckley DN and Moulin DE
Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current drugs used to treat fibromyalgia provide meaningful benefit to only 30-60% of treated individuals. Combining two or more different drugs is common in clinical practice with the expectation of better efficacy, tolerability or both; however, further research is needed to identify which combinations actually provide added benefit. Thus, we are planning a clinical trial to evaluate melatonin (MLT)-pregabalin (PGB) combination in participants with fibromyalgia.
TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer's disease
Vuoksimaa E, Saari TT, Aaltonen A, Aaltonen S, Herukka SK, Iso-Markku P, Kokkola T, Kyttälä A, Kärkkäinen S, Liedes H, Ollikainen M, Palviainen T, Ruotsalainen I, Toivola A, Urjansson M, Vasankari T, Vähä-Ypyä H, Forsberg MM, Hiltunen M, Jalanko A, Kälviäinen R, Kuopio T, Lähteenmäki J, Nyberg P, Männikkö M, Serpi R, Siltanen S, Palotie A, Kaprio J, Runz H, Julkunen V and
A better understanding of the earliest stages of Alzheimer's disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among THL Biobank donors according to TWINGEN study criteria.
Placebo effects in randomized trials of pharmacological and neurostimulation interventions for mental disorders: An umbrella review
Huneke NTM, Amin J, Baldwin DS, Bellato A, Brandt V, Chamberlain SR, Correll CU, Eudave L, Garner M, Gosling CJ, Hill CM, Hou R, Howes OD, Ioannidis K, Köhler-Forsberg O, Marzulli L, Reed C, Sinclair JMA, Singh S, Solmi M and Cortese S
There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed evidence across mental disorders. We carried out an umbrella review of meta-analyses of randomized controlled trials (RCTs) of biological treatments (pharmacotherapy or neurostimulation) for mental disorders. We explored whether placebo effect size differs across distinct disorders, and the correlates of increased placebo effects. Based on a pre-registered protocol, we searched Medline, PsycInfo, EMBASE, and Web of Knowledge up to 23.10.2022 for systematic reviews and/or meta-analyses reporting placebo effect sizes in psychopharmacological or neurostimulation RCTs. Twenty meta-analyses, summarising 1,691 RCTs involving 261,730 patients, were included. Placebo effect size varied, and was large in alcohol use disorder (g = 0.90, 95% CI [0.70, 1.09]), depression (g = 1.10, 95% CI [1.06, 1.15]), restless legs syndrome (g = 1.41, 95% CI [1.25, 1.56]), and generalized anxiety disorder (d = 1.85, 95% CI [1.61, 2.09]). Placebo effect size was small-to-medium in obsessive-compulsive disorder (d = 0.32, 95% CI [0.22, 0.41]), primary insomnia (g = 0.35, 95% CI [0.28, 0.42]), and schizophrenia spectrum disorders (standardized mean change = 0.33, 95% CI [0.22, 0.44]). Correlates of larger placebo response in multiple mental disorders included later publication year (opposite finding for ADHD), younger age, more trial sites, larger sample size, increased baseline severity, and larger active treatment effect size. Most (18 of 20) meta-analyses were judged 'low' quality as per AMSTAR-2. Placebo effect sizes varied substantially across mental disorders. Future research should explore the sources of this variation. We identified important gaps in the literature, with no eligible systematic reviews/meta-analyses of placebo response in stress-related disorders, eating disorders, behavioural addictions, or bipolar mania.
Prevalence of mental, behavioural or neurodevelopmental disorders according to the International Classification of Diseases 11: a scoping review protocol
Nafarieh K, Krüger S, Deutscher K, Schreiter S, Jung A, Fazel S, Heinz A and Gutwinski S
Due to a change in diagnostic prerequisites and the inclusion of novel diagnostic entities, the implementation of the 11th revision of the International Classification of Diseases (ICD-11) will presumably change prevalence rates of specific mental, behavioural or neurodevelopmental disorders and result in an altered prevalence rate for this grouping overall. This scoping review aims to summarise the characteristics of primary studies examining the prevalence of mental, behavioural or neurodevelopmental disorders based on ICD-11 criteria. The knowledge attained through this review will primarily characterise the methodological approaches of this research field and additionally assist in deciding which psychiatric diagnoses are-given the current literature-most relevant for subsequent systematic reviews and meta-analyses intended to approximate the magnitude of prevalence rates while providing a first glimpse of the range of expected (differences in) prevalence rates in these conditions.
Trying to forget alcohol: Brain mechanisms underlying memory suppression in young binge drinkers
Almeida-Antunes N, Antón-Toro L, Crego A, Rodrigues R, Sampaio A and López-Caneda E
People are able to voluntarily suppress unwanted thoughts or memories, a phenomenon known as suppression-induced forgetting or memory suppression. Despite harmful alcohol use, such as binge drinking, has been linked to impaired inhibitory control (IC) and augmented alcohol-cue reactivity, no study to date has assessed memory inhibition abilities towards alcohol-related cues in binge drinkers (BDs). Thus, the present preregistered study aimed to evaluate the behavioral and neurofunctional mechanisms associated with memory inhibition, specifically those related to the suppression of alcohol-related memories, in young BDs. For this purpose, electroencephalographic activity was recorded in eighty-two college students aged between 18 and 24 years old from the University of Minho (50% females; 40 non/low-drinkers [N/LDS] and 42 BDs) while they performed the Think/No-Think Alcohol task. Brain functional connectivity (FC) was calculated using the phase locking value and, subsequently, a dynamic seed-based analysis was conducted to explore the FC patterns between IC and memory networks. Comparatively to N/LDs, BDs exhibited decreased alpha-band FC between the anterior cingulate cortex and the left fusiform gyrus during attempts to suppress non-alcohol memories, accompanied by unsuccessful forgetting of those memories. Conversely, BDs displayed augmented gamma-band FC between the IC network and memory regions -i.e., hippocampus, parahippocampus and fusiform gyrus- during suppression of alcohol-related memories. Inhibitory abnormalities in BDs may lead to hypoconnectivity between IC and memory networks and deficient suppression of non-alcohol-related memories. However, while suppressing highly salient and reward-predicting stimuli, such as alcohol-related memories, BDs display a hyperconnectivity pattern between IC and memory networks, likely due to their augmented attention towards intrusive alcoholic memories and the attempts to compensate for potential underlying IC deficits. These findings hold important implications for alcohol research and treatment, as they open up new avenues for reducing alcohol use by shifting the focus to empowering suppression/control over alcohol-related memories. CLINICAL TRIAL REGISTRATION: [http://www.ClinicalTrials.gov], identifier [NCT05237414].
From Detection to Decision: How STIR Sequence MRI Influences Treatment Strategies for Osteoporotic Vertebral Fractures
Viola R, Aslan S, Al-Smadi MW, Süvegh D and Viola Á
Osteoporotic vertebral fractures (OVFs) significantly impair quality of life. This study evaluates the impact of STIR sequence MR imaging on clinical decision-making for treating OVFs, mainly focusing on how MRI findings influence treatment modifications compared to those based solely on CT scans. This retrospective analysis reviewed cases from the Manninger Jenő National Traumatology Institute over ten years, where patients with suspected OVFs underwent CT and STIR sequence MR imaging. The study examined changes in treatment plans initiated by MRI findings. The diagnostic effectiveness of MRI was compared against CT in terms of sensitivity, specificity, and the ability to influence clinical treatment paths. MRI detected 1.65 times more fractures than CT scans. MRI influenced treatment adjustments in 67% of cases, leading to significant changes from conservative-conservative, conservative-surgery, and surgery-surgery based on fracture characterizations provided by MRI. This study demonstrates that integrating STIR sequence MR imaging into the diagnostic pathway for OVFs significantly enhances the accuracy of fracture detection and profoundly impacts treatment decisions. The ability of MRI to reveal specific fracture features that are not detectable by CT scans supports its importance in the clinical evaluation of OVFs, suggesting that MRI should be incorporated more into diagnostic protocols to improve patient management and outcomes. The findings advocate for further research to establish STIR MRI as a standard osteoporosis management tool and explore its long-term benefits in preventing secondary fractures.
Transcutaneous auricular vagus nerve stimulation to acutely reduce emotional vulnerability and improve emotional regulation in borderline personality disorder (tVNS-BPD): study protocol for a randomized, single-blind, sham-controlled trial
Guerriero G, Liljedahl SI, Carlsen HK, López Muñoz M, Daros AR, Ruocco AC and Steingrimsson S
Borderline personality disorder (BPD) is considered a disorder of emotion regulation resulting from the expression of a biologically determined emotional vulnerability (that is, heightened sensitivity to emotion, increased emotional intensity/reactivity, and a slow return to emotional baseline) combined with exposure to invalidating environments. Vagal tone has been associated with activity in cortical regions involved in emotion regulation and a lower resting state of vagal tone has been observed in BPD patients relative to healthy controls. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has been shown to reduce temper outbursts in adults with Prader-Willi Syndrome, to enhance recognition of emotions in healthy students, and to improve depressive and anxiety symptoms. Furthermore, a single session of taVNS has been shown to acutely alter the recognition of facial expressions of negative valence in adolescents with MDD and increase emotion recognition in controls. However, the effect of taVNS on emotional vulnerability and regulation in individuals diagnosed with BPD has not been investigated. Our aims are to determine if taVNS is effective in acutely reducing emotional vulnerability and improve emotional regulation in BPD patients.
Near real-time patient experience feedback with data relay to providers: a systematic review of its effectiveness
Jesus TS, Struhar J, Zhang M, Lee D, Stern BZ, Heinemann AW, Jordan N and Deutsch A
Near Real-Time Feedback (NRTF) on the patient's experience with care, coupled with data relay to providers, can inform quality-of-care improvements, including at the point of care. The objective is to systematically review contemporary literature on the impact of the use of NRTF and data relay to providers on standardized patient experience measures. Six scientific databases and five specialty journals were searched supplemented by snowballing search strategies, according to the registered study protocol. Eligibility included studies in English (2015-2023) assessing the impact of NRTF and data relay on standardized patient-reported experience measures as a primary outcome. Eligibility and quality appraisals were performed by two independent reviewers. An expert former patient (Patient and Family Advisory Council and communication sciences background) helped interpret the results. Eight papers met review eligibility criteria, including three randomized controlled trials (RCTs) and one non-randomized study. Three of these studies involved in-person NRTF prior to data relay (patient-level data for immediate corrective action or aggregated and peer-compared) and led to significantly better results in all or some of the experience measures. In turn, a kiosk-based NRTF achieved no better experience results. The remaining studies were pre-post designs with mixed or neutral results and greater risks of bias. In-person NRTF on the patient experience followed by rapid data relay to their providers, either patient-level or provider-level as peer-compared, can improve the patient experience of care. Reviewed kiosk-based or self-reported approaches combined with data relay were not effective. Further research should determine which approach (e.g. who conducts the in-person NRTF) will provide better, more efficient improvements and under which circumstances.
Correction: Study protocol for pragmatic trials of Internet-delivered guided and unguided cognitive behavior therapy for treating depression and anxiety in university students of two Latin American countries: the Yo Puedo Sentirme Bien study
Benjet C, Kessler RC, Kazdin AE, Cuijpers P, Albor Y, Tapias NC, Contreras-Ibáñez CC, González MSD, Gildea SM, González N, López JBG, Luedtke A, Medina-Mora ME, Palacios J, Richards D, Salamanca-Sanabria A and Sampson NA
Study on the efficiency of virtual reality in the treatment of alcohol use disorder: study protocol for a randomized controlled trial : E-Reva
Nègre F, Lemercier-Dugarin M, Gomet R, Pelissolo A, Malbos E, Romo L and Zerdazi EH
According to the World Health Organization, alcohol is a major global public health problem, leading to a significant increase in illness and death. To treat alcohol use disorders, new therapeutic tools are being promoted, among which virtual reality (VR) shows promise. Previous research has demonstrated the efficacy of VR in reducing alcohol cravings in patients, but there is a lack of data on its effectiveness in maintaining abstinence or reducing consumption in recently abstinent individuals. The E-Reva study aims to compare the efficacy of a treatment strategy combining virtual reality cue exposure therapy (VR-CET) and cognitive behavioral therapy (CBT) with conventional CBT in reducing alcohol consumption and craving in patients with alcohol use disorder (AUD). In addition to this primary objective, the study will compare the effects of VR-CET combined with CBT on anxiety, depression, rumination, and feelings of self-efficacy versus conventional CBT.
Attention Deficit Hyperactivity Disorder: A Risk Factor for Premature Discontinuation of Inpatient Opioid Withdrawal Treatment
Gaspar N, Kilarski LL, Rosen H, Huppertz M, Philipsen A and Rohner H
: Substance use disorders present a tremendous challenge within contemporary healthcare systems. Specifically, in the domain of opioid use disorders (OUDs), several foundational elements are crucial for the efficacious management of afflicted individuals. Regrettably, the premature discontinuation of inpatient opioid withdrawal treatment is a prevalent phenomenon. This study aims to elucidate the prevalence of the premature termination of inpatient opioid withdrawal treatment among patients with comorbid ADHD. : We conducted a comprehensive assessment of all participants currently undergoing inpatient opioid withdrawal treatment. Our assessment protocol included the administration of the ADHD Self-Report Scale (ADHD-SR) and the Wender Utah Rating Scale (WURS-k). Additionally, participants who met the thresholds on one or both questionnaires underwent further evaluation using the Diagnostic Interview for ADHD in Adults (DIVA-2.0). : The prevalence of individuals diagnosed with ADHD within the studied cohort was determined to be 29.3%. Among the subset of participants identified as ADHD-positive, a notable 54.5% prematurely ceased therapy. In contrast, among those identified as ADHD-negative, the premature discontinuation rate was substantially lower at 28.3%. : In summary, the impact of ADHD as a comorbid condition on the efficacy of inpatient opioid withdrawal treatment has been underscored. By identifying comorbid ADHD early in the treatment process, tailored therapeutic approaches may help to maximize the effectiveness of interventions and may improve patient outcomes. This underscores the importance of proactive screening for ADHD as a psychiatric comorbidity in optimizing the management of individuals undergoing inpatient opioid withdrawal treatment.
Scalable Transdiagnostic Early Assessment of Mental Health (STREAM): a study protocol
Williams EH, Thompson NM, McCray G, Crespo-Llado MM, Bhavnani S, Gajria D, Mukherjee D, Del Bianco T, Lockwood-Estrin G, Mason L, Ngoma V, Namathanga C, Nkhata R, Bennie A, Ranjan A, Kawelama U, Midha N, Singh A, Mpakiza I, Gautam A, Gulati S, Johnson MH, Lancaster G, Belmonte MK, Jones E, Patel V, Chandran S, Mbale E, Divan G, Gladstone M and Chakrabarti B
Early childhood development forms the foundations for functioning later in life. Thus, accurate monitoring of developmental trajectories is critical. However, such monitoring often relies on time-intensive assessments which necessitate administration by skilled professionals. This difficulty is exacerbated in low-resource settings where such professionals are predominantly concentrated in urban and often private clinics, making them inaccessible to many. This geographic and economic inaccessibility contributes to a significant 'detection gap' where many children who might benefit from support remain undetected. The Scalable Transdiagnostic Early Assessment of Mental Health (STREAM) project aims to bridge this gap by developing an open-source, scalable, tablet-based platform administered by non-specialist workers to assess motor, social and cognitive developmental status. The goal is to deploy STREAM through public health initiatives, maximising opportunities for effective early interventions.
Effects of cerebellar repetitive transcranial magnetic stimulation plus physiotherapy in spinocerebellar ataxias - A randomized clinical trial
Grobe-Einsler M, Bork F, Faikus A, Hurlemann R and Kaut O
In absence of drug therapy options, standard treatment for spinocerebellar ataxia consists of symptomatic physiotherapy and speech therapy. New therapeutic options are urgently needed. Transcranial magnetic stimulation is a promising therapeutic option, but applicability is limited by lengthy duration of stimulation protocols.
The Effects of Transcranial Direct Current Stimulation (tDCS) in HIV Patients-A Review
Chmiel J, Kurpas D, Rybakowski F and Leszek J
: HIV is a severe and incurable disease that has a devastating impact worldwide. It affects the immune system and negatively affects the nervous system, leading to various cognitive and behavioral problems. Scientists are actively exploring different therapeutic approaches to combat these issues. One promising method is transcranial direct current stimulation (tDCS), a non-invasive technique that stimulates the brain. : This review aims to examine how tDCS can help HIV patients. Searches were conducted in the Pubmed/Medline, Research Gate, and Cochrane databases. : The literature search resulted in six articles focusing on the effects of tDCS on cognitive and behavioral measures in people with HIV. In some cases, tDCS showed positive improvements in the measures assessed, improving executive functions, depression, attention, reaction time, psychomotor speed, speed of processing, verbal learning and memory, and cognitive functioning. Furthermore, the stimulation was safe with no severe side effects. However, the included studies were of low quality, had small sample sizes, and did not use any relevant biomarkers that would help to understand the mechanisms of action of tDCS in HIV. : tDCS may help patients with HIV; however, due to the limited number of studies and the diversity of protocols used, caution should be exercised when recommending this treatment option in clinical settings. More high-quality research, preferably involving neurophysiological and neuroimaging measurements, is necessary to better understand how tDCS works in individuals with HIV.
Pregnancy and birth complications and long-term maternal mental health outcomes: A systematic review and meta-analysis
Bodunde EO, Buckley D, O'Neill E, Al Khalaf S, Maher GM, O'Connor K, McCarthy FP, Kublickiene K, Matvienko-Sikar K and Khashan AS
Few studies have examined the associations between pregnancy and birth complications and long-term (>12 months) maternal mental health outcomes.
Protocol for the development of a reporting guideline for umbrella reviews on epidemiological associations using cross-sectional, case-control and cohort studies: the Preferred Reporting Items for Umbrella Reviews of Cross-sectional, Case-control and Cohort studies (PRIUR-CCC)
Solmi M, Cobey K, Moher D, Ebrahimzadeh S, Dragioti E, Shin JI, Radua J, Cortese S, Shea B, Veronese N, Hartling L, Pollock M, Egger M, Papatheodorou S, Ioannidis JP and Carvalho AF
Observational studies are fraught with several biases including reverse causation and residual confounding. Overview of reviews of observational studies (ie, umbrella reviews) synthesise systematic reviews with or without meta-analyses of cross-sectional, case-control and cohort studies, and may also aid in the grading of the credibility of reported associations. The number of published umbrella reviews has been increasing. Recently, a reporting guideline for overviews of reviews of healthcare interventions (Preferred Reporting Items for Overviews of Reviews (PRIOR)) was published, but the field lacks reporting guidelines for umbrella reviews of observational studies. Our aim is to develop a reporting guideline for umbrella reviews on cross-sectional, case-control and cohort studies assessing epidemiological associations.
Efficacy and Neural Mechanisms of Mindfulness Meditation Among Adults With Internet Gaming Disorder: A Randomized Clinical Trial
Ni H, Wang H, Ma X, Li S, Liu C, Song X, Potenza MN and Dong GH
The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), recently identified internet gaming disorder (IGD) as a condition warranting more research, and few empirically validated treatments exist. Mindfulness meditation (MM) has multiple health benefits; however, its efficacy in treating IGD and potential neural mechanisms underlying MM treatment of the disorder remain largely unknown.
Proof of mechanism investigation of Transcutaneous auricular vagus nerve stimulation through simultaneous measurement of autonomic functions: a randomized controlled trial protocol
Katsunuma R, Takamura T, Yamada M and Sekiguchi A
The autonomic nervous system plays a vital role in regulating physiological functions. Transcutaneous auricular vagus nerve stimulation (taVNS) is a method that provides insights into autonomic nerve modulation. This paper presents a research protocol investigating proof of mechanism for the impact of taVNS on autonomic functions and aims to both deepen theoretical understanding and pave the way for clinically relevant applications.
Efficacy and safety of omega-3 fatty acids supplementation for anxiety symptoms: a systematic review and dose-response meta-analysis of randomized controlled trials
Bafkar N, Zeraattalab-Motlagh S, Jayedi A and Shab-Bidar S
There is uncertainty about the optimum dose of omega-3 fatty acids for anxiety symptoms. We aimed to find the dose-dependent effect of omega-3 supplementation on anxiety symptoms.
Metabolic, cardiovascular, neuromuscular and perceptual responses to repeated military-specific load carriage treadmill simulations
Vine CAJ, Coakley SL, Blacker SD, Runswick OR and Myers SD
Bouts of military load carriage are rarely completed in isolation; however, limited research has investigated the physiological responses to repeated load carriage tasks. Twelve civilian men (age, 28 ± 8 years; stature, 185.6 ± 5.8 cm; body mass 84.3 ± 11.1 kg and maximal oxygen uptake, 51.5 ± 6.4 mL·kg min) attended the laboratory on two occasions to undertake a familiarisation and an experimental session. Following their familiarisation session, participants completed three bouts of a fast load carriage protocol (FLCP; ∼65 min), carrying 25 kg, interspersed with a 65-min recovery period. Physiological strain (oxygen uptake [V̇O] and heart rate [HR]) was assessed during the FLCP bouts, and physical performance assessments (weighted counter-movement jump [wCMJ], maximal isometric voluntary contraction of the quadriceps [MIVC] and seated medicine ball throw [SMBT]) was measured pre and post each FLCP bout. A main effect for bout and measurement time was evident for V̇O and HR (both p < 0.001 and Ѡ = 0.103-0.816). There was no likely change in SMBT distance (p = 0.201 and Ѡ = 0.004), but MIVC peak force reduced by approximately 25% across measurement points (p < 0.001 and Ѡ = 0.133). A mean percentage change of approximately -12% from initial values was also evident for peak wCMJ height (p = 0.001 and Ѡ = 0.028). Collectively, these data demonstrate that repeated FLCP bouts result in an elevated physiological strain for each successive bout, along with a substantial reduction in lower body power (wCMJ and MIVC). Therefore, future research should investigate possible mitigation strategies to maintain role-related capability.
Effects of brief family psychoeducation on family caregiver burden of people with schizophrenia provided by psychiatric visiting nurses: a cluster randomised controlled trial
Yasuma N, Sato S, Yamaguchi S, Matsunaga A, Shiozawa T, Tachimori H, Watanabe K, Imamura K, Nishi D, Fujii C and Kawakami N
The purpose of this study was to examine the effects of a brief family psychoeducation (BFP) programme provided by psychiatric visiting nurses on caregiver burden of family caregivers of people with schizophrenia through a cluster randomised controlled trial (cRCT).
Personalized brain circuit scores identify clinically distinct biotypes in depression and anxiety
Tozzi L, Zhang X, Pines A, Olmsted AM, Zhai ES, Anene ET, Chesnut M, Holt-Gosselin B, Chang S, Stetz PC, Ramirez CA, Hack LM, Korgaonkar MS, Wintermark M, Gotlib IH, Ma J and Williams LM
There is an urgent need to derive quantitative measures based on coherent neurobiological dysfunctions or 'biotypes' to enable stratification of patients with depression and anxiety. We used task-free and task-evoked data from a standardized functional magnetic resonance imaging protocol conducted across multiple studies in patients with depression and anxiety when treatment free (n = 801) and after randomization to pharmacotherapy or behavioral therapy (n = 250). From these patients, we derived personalized and interpretable scores of brain circuit dysfunction grounded in a theoretical taxonomy. Participants were subdivided into six biotypes defined by distinct profiles of intrinsic task-free functional connectivity within the default mode, salience and frontoparietal attention circuits, and of activation and connectivity within frontal and subcortical regions elicited by emotional and cognitive tasks. The six biotypes showed consistency with our theoretical taxonomy and were distinguished by symptoms, behavioral performance on general and emotional cognitive computerized tests, and response to pharmacotherapy as well as behavioral therapy. Our results provide a new, theory-driven, clinically validated and interpretable quantitative method to parse the biological heterogeneity of depression and anxiety. Thus, they represent a promising approach to advance precision clinical care in psychiatry.
A Scoping Review of PTSD and Depression in Adult Burn Patients: A Call for Standardized Screening and Intervention Research
Wang S, Cannata B, Vallurupalli M, Yenikomshian HA, Gillenwater TJ and Stoycos SA
Despite the growing incidence of burn injuries globally and the advancements in physical recovery, the psychological aspect of burn trauma recovery remains inadequately addressed. This review aims to consolidate existing literature posttraumatic stress disorder (PTSD) and depression in adult burn survivors, recognizing the need for a holistic approach to burn recovery that encompasses both physical and mental health. The comprehensive analysis of 156 studies revealed significant variations in methodological approaches, leading to challenges in creating standardized protocols for mental health assessment in burn care. Key findings include the identification of a wide range of psychological assessment tools and a substantial research gap in low and middle-income countries, where the majority of burn injuries occur. Only 7.0% of the studies assessed interventions for PTSD or depression, indicating a lack of focus on treatment modalities. The studies identified demographic factors, patient history, psychosocial factors, burn injury characteristics, and treatment course as risk factors for PTSD and depression post-burn injury. The review highlights the need for early screening, intervention, and attention to subjective experiences related to burn injury, as these are strong predictors of long-term psychological distress. It also emphasizes the complexity of addressing psychological distress in burn survivors and the need for more standardized practices in assessing PTSD and depression specific to this population.
Antibiotics for delirium in older adults with pyuria or bacteriuria: A systematic review
Stall NM, Kandel C, Reppas-Rindlisbacher C, Quinn KL, Wiesenfeld L, MacFadden DR, Johnstone J and Fralick M
It is unclear whether antibiotics impact delirium outcomes in older adults with pyuria or bacteriuria in the absence of systemic signs of infection or genitourinary symptoms.
Blended Psychological Interventions for Emotional Disorders in Youth: Acceptability and Intention to Use in a Sample of Portuguese Psychologists
Gomes-Pereira B, Góis A, Pereira AM, Caiado B, Moreira H and Pereira AI
The rise of mental health problems in youth highlights the need for accessible and cost-effective psychological interventions. Blended interventions, which combine face-to-face and online sessions, can be an adequate response to the increase in demands for youth mental health services. Although this can be a promising approach, effective dissemination depends on the professionals´ acceptance.
"It was very nice to be in a room where everyone had ADD-that's kind of VIP": Exploring clients' perceptions of group CBT for ADHD inattentive presentation
Strålin EE, Sunnhed R, Thorell LB, Lundgren T, Bölte S and Bohman B
This qualitative study explored the perceptions of adult clients participating in a new psychological treatment for attention-deficit/hyperactivity disorder inattentive presentation (ADHD-I, also called "attention deficit disorder", ADD). The study aimed to explore (i) what aspects of treatment the participants found to be helpful, and (ii) if there were areas that ought to be developed to make the protocol more useful to clients with ADHD-I.
Latent class analysis and longitudinal development trajectory study of psychological distress in patients with stroke: a study protocol
Guo Y, Zhou M, Yan X, Liu Y and Wang L
Psychological distress affects the treatment and rehabilitation of patients with stroke, affects their long-term functional exercise and quality of life, and increases the risk of stroke recurrence and even death. This is a multi-dimensional and multi-level mental health problem and a dynamic process variable that shows a dynamic development trend with time. However, previous studies have been insufficient to deeply study the change mechanism of psychological distress, and there remains a lack of forward-looking longitudinal studies to analyze its change trajectory. This study aimed to investigate potential categories and how psychological distress changes over time and to examine conversion probability in these transformation processes.
Targeted psychological and psychosocial interventions for auditory hallucinations in persons with psychotic disorders: Protocol for a systematic review and meta-analysis
Fässler L, Bighelli I, Leucht S, Sabé M, Bajbouj M, Knaevelsrud C and Böge K
In recent years, a growing body of evidence has demonstrated the efficacy of non-pharmacological interventions for schizophrenia spectrum disorders (SSD) including positive symptoms such as auditory hallucinations (AH). However, clinical trials predominantly examine general treatment effects for positive symptoms. Therefore, previous research is lacking in comprehensive and clear evidence about psychological and psychosocial approaches that are primarily tailored to treat AH. To overcome this knowledge gap in the current literature, we will conduct a systematic review and meta-analysis to assess the efficacy of clearly targeted psychological and psychosocial interventions for AH in persons with SSD.
Investigating psychobiological causes and mechanisms in functional seizures and functional motor symptoms: Study protocol
Pick S, David AS, Edwards MJ, Goldstein LH, Hodsoll J, Millman LSM, Nicholson TR, Reinders AATS, Stanton B, Winston JS, Mehta MA, Chalder T and Hotopf M
Advances have been made in understanding the aetiology of functional neurological disorder (FND); however, its pathophysiological mechanisms have not been definitively demonstrated. Evidence suggests interacting roles for altered emotional processing and interoception, elevated autonomic arousal, and dissociation, but there is limited evidence demonstrating their causal influence on specific FND symptoms. Our superordinate aim is to elucidate potentially shared and distinct aetiological factors and mechanisms in two common FND subtypes, functional seizures (FS) and functional motor symptoms (FMS).
Optimizing outcomes when treating functional neurological disorder in acute care settings: case reports depicting the value of diagnostic precision and timely and appropriate psychological interventions using an interdisciplinary framework
Greenfield MJ, Fobian AD, Fargason RE and Birur B
Unexplained physical signs and symptoms represent a significant portion of patient presentations in acute care settings. Even in cases where a patient presents with a known medical condition, functional or somatic symptoms may complicate the diagnostic and treatment processes and prognostic outcome. One umbrella category for neurologically related somatic symptoms, functional neurological disorder (FND), presents as involuntary neurological symptoms incompatible with another medical condition. Symptoms may include weakness and/or paralysis, movement disorders, non-epileptic seizures, speech or visual impairment, swallowing difficulty, sensory disturbances, or cognitive symptoms (1). While FND presents as neuropsychiatric, providers commonly report feeling hesitant to diagnose these disorders. Inexperience or lack of appropriate education on relevant research regarding evidence-based practices or standard of practice (SOP) may result in over- or underperforming diagnostic workups and consultations, utilizing inappropriate medications, and failing to offer evidence-based psychological interventions. Being mindful of these challenges when treating patients presenting with functional symptoms in acute care settings can help to support and protect the patients and care team and appropriately control healthcare costs.
Investigating the neural mechanisms of transcranial direct current stimulation effects on human cognition: current issues and potential solutions
Meinzer M, Shahbabaie A, Antonenko D, Blankenburg F, Fischer R, Hartwigsen G, Nitsche MA, Li SC, Thielscher A, Timmann D, Waltemath D, Abdelmotaleb M, Kocataş H, Caisachana Guevara LM, Batsikadze G, Grundei M, Cunha T, Hayek D, Turker S, Schlitt F, Shi Y, Khan A, Burke M, Riemann S, Niemann F and Flöel A
Transcranial direct current stimulation (tDCS) has been studied extensively for its potential to enhance human cognitive functions in healthy individuals and to treat cognitive impairment in various clinical populations. However, little is known about how tDCS modulates the neural networks supporting cognition and the complex interplay with mediating factors that may explain the frequently observed variability of stimulation effects within and between studies. Moreover, research in this field has been characterized by substantial methodological variability, frequent lack of rigorous experimental control and small sample sizes, thereby limiting the generalizability of findings and translational potential of tDCS. The present manuscript aims to delineate how these important issues can be addressed within a neuroimaging context, to reveal the neural underpinnings, predictors and mediators of tDCS-induced behavioral modulation. We will focus on functional magnetic resonance imaging (fMRI), because it allows the investigation of tDCS effects with excellent spatial precision and sufficient temporal resolution across the entire brain. Moreover, high resolution structural imaging data can be acquired for precise localization of stimulation effects, verification of electrode positions on the scalp and realistic current modeling based on individual head and brain anatomy. However, the general principles outlined in this review will also be applicable to other imaging modalities. Following an introduction to the overall state-of-the-art in this field, we will discuss in more detail the underlying causes of variability in previous tDCS studies. Moreover, we will elaborate on design considerations for tDCS-fMRI studies, optimization of tDCS and imaging protocols and how to assure high-level experimental control. Two additional sections address the pressing need for more systematic investigation of tDCS effects across the healthy human lifespan and implications for tDCS studies in age-associated disease, and potential benefits of establishing large-scale, multidisciplinary consortia for more coordinated tDCS research in the future. We hope that this review will contribute to more coordinated, methodologically sound, transparent and reproducible research in this field. Ultimately, our aim is to facilitate a better understanding of the underlying mechanisms by which tDCS modulates human cognitive functions and more effective and individually tailored translational and clinical applications of this technique in the future.
Psychological intervention in women victims of childhood sexual abuse: a randomized controlled clinical trial comparing EMDR psychotherapy and trauma-focused cognitive behavioral therapy
Molero-Zafra M, Fernández-García O, Mitjans-Lafont MT, Pérez-Marín M and Hernández-Jiménez MJ
Childhood sexual abuse persists as a painful societal reality, necessitating responses from institutions and healthcare professionals to prevent and address its severe long-term consequences in victims. This study implements an intervention comprising two psychotherapeutic approaches recommended by the WHO and international clinical guidelines for addressing short-, medium-, and long-term posttraumatic symptomatology: Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) and Eye Movement Desensitization and Reprocessing (EMDR). Both approaches are adapted from group formats for implementation in small online groups via Zoom.
Bovine colostrum supplementation as a new perspective in depression and substance use disorder treatment: a randomized placebo-controlled study
Durkalec-Michalski K, Główka N, Podgórski T, Odrobny W, Krawczyński M, Botwina R, Bodzicz S and Nowaczyk PM
This randomized, placebo-controlled, double-blind, parallel study aimed to evaluate the effect of 3-month supplementation of bovine colostrum (BOV-COL; 8400 mg per day) on the outcomes of depression treatment in hospitalized patients with substance use disorder (SUD). The hypothesis is that BOV-COL supplementation as an add-on treatment results in favorable alternations in selected blood inflammatory markers or neurotransmitters, leading to better depression treatment outcomes compared with placebo (PLA).
Evaluating a mobile-based intervention to promote the mental health of informal dementia caregivers in Singapore: Study protocol for a pilot two-armed randomised controlled trial
Lee YT, Yuan Q, Zhang Y, Samari E, Goveas R, Ng LL and Subramaniam M
Informal caregivers of persons with dementia (PWD) often suffer adverse impacts on their mental health and require interventions for effective support. As they are often occupied with providing care, web-based interventions could be more convenient and efficient for them. However, there is currently a dearth of evidence-based mobile interventions to enhance the mental well-being of dementia caregivers locally, especially ones that are user-centered and culturally relevant. Hence, having designed an app based on feedback from local dementia caregivers, this study will evaluate the effectiveness of this mobile app in promoting the mental health of informal caregivers of PWD in Singapore.
What do older adults want from spine care?
Weiser S, Mowery HC, Campello M, Chytas V and Cedraschi C
Older adults comprise a large portion of back pain (BP) sufferers but are under-represented in the literature. Patients over age 65 present with different clinical characteristics and psychosocial needs than younger patients. Therefore, recommended patient-centered outcomes for BP may not be relevant to older patients.
Systematic review and meta-analysis on the effect of depression on ART adherence among women living with HIV
Zeleke TA, Alemu K, Ayele TA, Denu ZA, Mwanri L and Azale T
Depression is a very common psychiatric disorder in worldwide. Globally, Human Immunodeficiency Virus (HIV) is highly prevalent among women, and are disproportionately affected by depression. Antiretroviral Therapy (ART) adherence which could highly be affected by depression is yet to be explored effectively. Depression affects overall poor HIV clinical outcomes, socioeconomic and social interactions. However, it is not well understood specifically how depression affects ART adherence in women living with HIV (WLWHIV). Investigating the effects of depression on ART adherence is critical in order to develop nuanced new evidence to address non-adherence in WLWHIV.
Perinatal mental disorders and suicidal risk among adolescent mothers living in urban areas of Cameroon
Miafo JD, Nzebou D, Stoll B, Yimga Ngambia JC, von Overbeck Ottino S and Moayedoddin A
In sub-Saharan Africa the birth rate among teenage mothers is the highest in the world. In 2021, there would be 6,114,000 births for 15-19-year-olds in this part of the world. In Cameroon, the fertility rate among adolescents aged 15-19 is 24%. However, there is a significant lack of data on the mental health of teenage mothers. Given the biopsychosocial conditions of the perinatal period and adolescence, we hypothesise that the prevalence of mental disorders and the risk of suicide is very high in Cameroon. The aim is therefore to determine the prevalence of perinatal mental disorders and suicide risk among adolescent mothers in urban areas of Cameroon.
Influence of frailty on cardiovascular events and mortality in patients with Chronic Obstructive Pulmonary Disease (COPD): Study protocol for a multicentre European observational study
Verduri A, Clini E, Carter B and Hewitt J
Frailty is a clinical state that increases susceptibility to minor stressor events. The risk of frailty is higher in chronic conditions, such as Chronic Obstructive Pulmonary Disease (COPD). Recent studies on COPD have shown that patients living with frailty have an increased risk of mortality. The presence of cardiovascular diseases or conditions are common in COPD and may increase the risk of death.
Book-Sharing for Toddlers with Clefts (BOOST): Protocol for a randomized controlled trial of a remote intervention to promote language development in children with cleft palate
Collett BR, Gallagher ER, Johns AL, Trevino CO, Leroux BG, Shic F, Crerand CE, Baylis AL, Cummings CA and Santillan L
Children with cleft palate, with or without cleft lip (CP±L), exhibit language delays on average compared to children without clefts. Interventions to address these disparities are scarce. In this multi-center study, Book Sharing for Toddlers with Clefts (BOOST), we will test a remote, parent-focused intervention to promote language development in children with CP±L.
Recent treatment and novel imaging studies evaluating treatment of internet gaming disorder: a narrative review
Sharma R and Weinstein AM
Internet Gaming Disorder (IGD) is an emerging public health concern; effective treatments are still under development. This mini-review focuses on summarizing the main scientific evidence from psychological, pharmacological, brain imaging, and emerging treatment approaches for IGD. We searched PubMed and Scopus databases using keywords related to IGD and treatment. Cognitive behavioral therapy (CBT) is the most extensively researched psychological treatment for IGD, supported by several randomized controlled trials (RCTs). Other promising approaches include mindfulness, relapse prevention, abstinence protocols, and family therapy. Pharmacological treatments like bupropion and escitalopram have shown benefits, especially when IGD is comorbid with conditions like major depressive disorder. However, the quality of evidence is moderate for psychological interventions but low to moderate for pharmacological approaches. Emerging treatments such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and electro-acupuncture have demonstrated efficacy in reducing IGD symptoms and modulating brain activity. Brain imaging techniques like functional magnetic resonance imaging (fMRI) have provided insights into the neural mechanisms underlying IGD and treatment effects, although these studies lack randomized controlled designs. While multimodal approaches show promise, larger, well-designed RCTs are needed to establish effective IGD treatments.
Electroconvulsive therapy for the acute management of severe agitation in dementia (ECT-AD): A modified study protocol
Lapid MI, Merrill J, Mueller M, Hermida AP, Nykamp L, Andrus J, Azizi H, Bolton P, Bonsu N, Braga R, Dillon CR, Ecklesdafer D, Evans D, Harper D, Heintz H, Hussain-Krauter S, Holzgen O, Humphrey D, Jiwani S, Johnson EK, Kang S, Kassien J, Kim J, Knapp RG, Kung S, Kremen N, Le K, Mahdasian J, Marzouk T, Masrud JD, Mattingly J, Miller D, Pagali SR, Patrick R, Riva Posse P, Pritchett C, Rahman A, Rath S, Roczniak C, Rummans TA, Sanghani S, Seiner S, Smart L, Tomaschek E, Tsygankova V, VanderSchuur-White L, Walton MP, Wilkins J, Williams A, Williams SM, Petrides G and Forester BP
This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe treatment-refractory agitation in advanced dementia. The aims are to assess agitation reduction using the Cohen-Mansfield Agitation Inventory (CMAI), evaluate tolerability and safety outcomes, and explore the long-term stability of agitation reduction and global functioning. Due to challenges encountered during implementation, including recruitment obstacles and operational difficulties, the study design was modified to an open-label format and other protocol amendments were implemented.
Bradykinesia in dystonic hand tremor: kinematic analysis and clinical rating
Matejicka P, Kajan S, Goga J, Straka I, Balaz M, Janovic S, Minar M, Valkovic P, Hajduk M and Kosutzka Z
Bradykinesia is an essential diagnostic criterion for Parkinson's disease (PD) but is frequently observed in many non-parkinsonian movement disorders, complicating differential diagnosis, particularly in disorders featuring tremors. The presence of bradykinetic features in the subset of dystonic tremors (DT), either "pure" dystonic tremors or tremors associated with dystonia, remains currently unexplored. The aim of the current study was to evaluate upper limb bradykinesia in DT patients, comparing them with healthy controls (HC) and patients with PD by observing repetitive finger tapping (FT).
Does a single session of transcranial direct current stimulation enhance both physical and psychological performance in national- or international-level athletes? A systematic review
Yu Y, Zhang X, Nitsche MA, Vicario CM and Qi F
Some studies showed that a single session of transcranial direct current stimulation (tDCS) has the potential of modulating motor performance in healthy and athletes. To our knowledge, previously published systematic reviews have neither comprehensively investigated the effects of tDCS on athletic performance in both physical and psychological parameters nor investigated the effects of tDCS on high-level athletes. We examined all available research testing a single session of tDCS on strength, endurance, sport-specific performance, emotional states and cognitive performance for better application in competition and pre-competition trainings of national- or international-level athletes. A systematic search was conducted in PubMed, Web of Science, EBSCO, Embase, and Scopus up until to June 2023. Studies were eligible when participants had sports experience at a minimum of state and national level competitions, underwent a single session of tDCS without additional interventions, and received either sham tDCS or no interventions in the control groups. A total of 20 experimental studies (224 participants) were included from 18 articles. The results showed that a single tDCS session improved both physical and psychological parameters in 12 out of the 18 studies. Of these, six refer to the application of tDCS on the motor system (motor cortex, premotor cortex, cerebellum), five on dorsolateral prefrontal cortex and two on temporal cortex. The most sensitive to tDCS are strength, endurance, and emotional states, improved in 67%, 75%, and 75% of studies, respectively. Less than half of the studies showed improvement in sport-specific tasks (40%) and cognitive performance (33%). We suggest that tDCS is an effective tool that can be applied to competition and pre-competition training to improve athletic performance in national- or international-level athletes. Further research would explore various parameters (type of sports, brain regions, stimulation protocol, athlete level, and test tasks) and neural mechanistic studies in improving efficacy of tDCS interventions. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326989, identifier CRD42022326989.
Delirium management in perioperative geriatric services: a narrative review of non-pharmaceutical strategies
Travers R, Gagliardi G and Ramseyer M
Delirium, a common complication in elderly surgical patients, poses significant challenges in perioperative care. Perioperative geriatric services (PGS) aim at managing comorbidities, postoperative complications, and initiating early recovery of mobility to enhance elderly patients' prognosis in the perioperative period. Studies have shown that patients with preoperative cognitive disorders are at a significantly increased risk of postoperative delirium. While postoperative delirium affects up to 70% of people over 60 and 90% of people with neurodegenerative diseases, it remains underdiagnosed in many cases. Postoperative delirium can lead to functional decline, prolonged hospitalization, increased healthcare costs, cognitive impairment, and psychological malaise. This article briefly summarizes the literature on delirium, its risk factors, and its non-pharmaceutical management strategies within the perioperative period. It highlights the importance of integrating cognitive and psychological assessments into perioperative care protocols to provide baseline data, improve patient outcomes, reduce hospital stays, and minimize complications associated with delirium. By embracing evidence-based delirium management protocols, healthcare professionals can better identify and manage delirium, ultimately improving the quality of care for elderly surgical patients, which would also benefit healthcare staff and healthcare institutions.
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